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| Status |
Public on Jul 31, 2018 |
| Title |
The DiGeorge Syndrome gene TBX1 is required to specify the nkx2.5+ cardiopharyngeal lineage |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hemizygous microdeletions on chromosome 22q11.2 cause a broad spectrum of congenital cardiovascular and craniofacial anomalies known collectively as DiGeorge Syndrome (DGS) that appear to arise from reduced expression of TBX1, a gene in the typically deleted region. Although mice lacking tbx1 display similar, yet more severe, cardiovascular and craniofacial defects, the mechanisms underlying these devastating phenotypes remain incompletely understood. Here, we report that Tbx1 is required prior to pharyngeal arch development to specify the nkx2.5+ cardiopharyngeal cell lineage that gives rise to the cardiovascular and crainiofacial structures absent in tbx1 null zebrafish. Importantly, the role of Tbx1 during cardiopharyngeal lineage specification is conserved in mammals. Further, we learned that DVR1, the zebrafish homolog of mammalian GDF1/3, functions downstream of Tbx1 for pharyngeal progenitor specification. Together, these studies unveil a new paradigm potentially underlying the cardiovascular and craniofacial defects observed in the DGS population.
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| Overall design |
Determination of differentially expressed genes/pathways between tbx1 mutants and controls.
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| |
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| Contributor(s) |
Guner-Ataman B, Burns CG, Burns CE |
| Citation(s) |
30067987 |
| |
| Submission date |
Aug 25, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Caroline Burns |
| E-mail(s) |
CBURNS6@mgh.harvard.edu
|
| Organization name |
Massachusetts General Hospital, Harvard Medical School
|
| Department |
Cardiovascular Research Center
|
| Lab |
Harvard Stem Cell Institute
|
| Street address |
CVRC, 4th floor, 4138E 149 13th Street
|
| City |
Charlestown |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA400209 |
| SRA |
SRP116195 |
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